title: Can phylogenetic type predict resistance development?
abstract: OBJECTIVE
  To determine whether phylogenetic type is associated with the development of multidrug resistance to antibiotics.
  
  
  METHODS
  Urinary tract infection (UTI) isolates from three hospitals in Pakistan were collected over a period of 10 months, and analysed in terms of causative bacterial species and drug susceptibility.
  
  
  RESULTS
  Multidrug resistance was widespread and resistance frequencies were >50% for several of the most commonly used antibiotics, including ciprofloxacin and third-generation cephalosporins for Escherichia coli isolates. The great majority of E. coli isolates remained susceptible to meropenem and fosfomycin. Sixty E. coli isolates were analysed in detail to determine correlations between resistance phenotypes and genotypes, mutation rates and phylogenetic group. Most isolates had elevated mutation rates, suggesting this was being selected. The majority of ciprofloxacin-resistant isolates carried a specific set of mutations in the quinolone resistance-determining region of gyrA and parC (S83L, D87N, S80I and E84V). In addition, 67% of the ciprofloxacin-resistant E. coli isolates carried one or more horizontally transmissible determinants of resistance to ciprofloxacin, including aac(6')-Ib-cr, qepA, qnrA and qnrB. There was a significant correlation between resistance to third-generation cephalosporins, being an extended-spectrum β-lactamase producer, being resistant to ciprofloxacin and belonging to phylogenetic group B2.
  
  
  CONCLUSIONS
  The data suggest that features of the bacterial genotype might facilitate the development of multidrug resistance in particular lineages. Better understanding of the mechanistic basis for correlations between drug resistance and genotype could potentially be exploited to develop molecular tools for the prediction of resistance development.
authors.affiliation: Department of Cell and Molecular Biology, Uppsala University, Box 596, Biomedical Center, SE-75124 Uppsala, Sweden.
authors.forename: Humera
authors.initials: H
authors.lastname: Nazir
authors.forename: Sha
authors.initials: S
authors.lastname: Cao
authors.forename: Fariha
authors.initials: F
authors.lastname: Hasan
authors.forename: Diarmaid
authors.initials: D
authors.lastname: Hughes
mesh_terms: D000328:Adult; D019943:Amino Acid Substitution / Q000235:genetics; D015373:Bacterial Typing Techniques; D024881:Drug Resistance, Bacterial; D004926:Escherichia coli / Q000145:classification* / Q000187:drug effects* / Q000235:genetics / Q000302:isolation & purification; D004927:Escherichia coli Infections / Q000382:microbiology; D029968:Escherichia coli Proteins / Q000235:genetics; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D058889:Molecular Typing; D020125:Mutation, Missense; D010154:Pakistan; D010802:Phylogeny; D014552:Urinary Tract Infections / Q000382:microbiology
chemical_list: D029968:Escherichia coli Proteins